arXiv subjects

Michael Lässig

Publications and source records attributed to Michael Lässig.

29 records · Page 2Linked to original sources

arXiv2006

Bayesian analysis of biological networks: clusters, motifs, cross-species correlations

An important part of the analysis of bio-molecular networks is to detect different functional units. Different functions are reflected in a different evolutionary dynamics, and hence in different statistical characteristics of network parts. In this sense, the {\em global statistics} of a biological network, e.g., its connectivity distribution, provides a background, and {\em local deviations} from this background signal functional units. In the computational analysis of biological networks, we thus typically have to discriminate between different statistical models governing different parts of the dataset. The nature of these models depends on the biological question asked. We illustrate this rationale here with three examples: identification of functional parts as highly connected \textit{network clusters}, finding \textit{network motifs}, which occur in a similar form at different places in the network, and the analysis of \textit{cross-species network correlations}, which reflect evolutionary dynamics between species.

q-bio.MN↗

arXiv2006

Cross-species analysis of biological networks by Bayesian alignment

Complex interactions between genes or proteins contribute a substantial part to phenotypic evolution. Here we develop an evolutionarily grounded method for the cross-species analysis of interaction networks by {\em alignment}, which maps bona fide functional relationships between genes in different organisms. Network alignment is based on a scoring function measuring mutual similarities between networks taking into account their interaction patterns as well as sequence similarities between their nodes. High-scoring alignments and optimal alignment parameters are inferred by a systematic Bayesian analysis. We apply this method to analyze the evolution of co-expression networks between human and mouse. We find evidence for significant conservation of gene expression clusters and give network-based predictions of gene function. We discuss examples where cross-species functional relationships between genes do not concur with sequence similarity.

q-bio.MN↗

arXiv2006

The Freezing of Random RNA

We study secondary structures of random RNA molecules by means of a renormalized field theory based on an expansion in the sequence disorder. We show that there is a continuous phase transition from a molten phase at higher temperatures to a low-temperature glass phase. The primary freezing occurs above the critical temperature, with local islands of stable folds forming within the molten phase. The size of these islands defines the correlation length of the transition. Our results include critical exponents at the transition and in the glass phase.

q-bio.BM↗

arXiv2005

Biodiversity in model ecosystems, I: Coexistence conditions for competing species

This is the first of two papers where we discuss the limits imposed by competition to the biodiversity of species communities. In this first paper we study the coexistence of competing species at the fixed point of population dynamic equations. For many simple models, this imposes a limit on the width of the productivity distribution, which is more severe the more diverse the ecosystem is (Chesson, 1994). Here we review and generalize this analysis, beyond the ``mean-field''-like approximation of the competition matrix used in previous works, and extend it to structured food webs. In all cases analysed, we obtain qualitatively similar relations between biodiversity and competition: the narrower the productivity distribution is, the more species can stably coexist. We discuss how this result, considered together with environmental fluctuations, limits the maximal biodiversity that a trophic level can host.

q-bio.PE↗

arXiv2005

Biodiversity in model ecosystems, II: Species assembly and food web structure

This is the second of two papers dedicated to the relationship between population models of competition and biodiversity. Here we consider species assembly models where the population dynamics is kept far from fixed points through the continuous introduction of new species, and generalize to such models thecoexistence condition derived for systems at the fixed point. The ecological overlap between species with shared preys, that we define here, provides a quantitative measure of the effective interspecies competition and of the trophic network topology. We obtain distributions of the overlap from simulations of a new model based both on immigration and speciation, and show that they are in good agreement with those measured for three large natural food webs. As discussed in the first paper, rapid environmental fluctuations, interacting with the condition for coexistence of competing species, limit the maximal biodiversity that a trophic level can host. This horizontal limitation to biodiversity is here combined with either dissipation of energy or growth of fluctuations, which in our model limit the length of food webs in the vertical direction. These ingredients yield an effective model of food webs that produce a biodiversity profile with a maximum at an intermediate trophic level, in agreement with field studies.

q-bio.PE↗

arXiv2005

A Solvable Sequence Evolution Model and Genomic Correlations

We study a minimal model for genome evolution whose elementary processes are single site mutation, duplication and deletion of sequence regions and insertion of random segments. These processes are found to generate long-range correlations in the composition of letters as long as the sequence length is growing, i.e., the combined rates of duplications and insertions are higher than the deletion rate. For constant sequence length, on the other hand, all initial correlations decay exponentially. These results are obtained analytically and by simulations. They are compared with the long-range correlations observed in genomic DNA, and the implications for genome evolution are discussed.

q-bio.GN↗

arXiv2004

Structure and evolution of protein interaction networks: A statistical model for link dynamics and gene duplications

The structure of molecular networks derives from dynamical processes on evolutionary time scales. For protein interaction networks, global statistical features of their structure can now be inferred consistently from several large-throughput datasets. Understanding the underlying evolutionary dynamics is crucial for discerning random parts of the network from biologically important properties shaped by natural selection. We present a detailed statistical analysis of the protein interactions in Saccharomyces cerevisiae based on several large-throughput datasets. Protein pairs resulting from gene duplications are used as tracers into the evolutionary past of the network. From this analysis, we infer rate estimates for two key evolutionary processes shaping the network: (i) gene duplications and (ii) gain and loss of interactions through mutations in existing proteins, which are referred to as link dynamics. Importantly, the link dynamics is asymmetric, i.e., the evolutionary steps are mutations in just one of the binding parters. The link turnover is shown to be much faster than gene duplications. According to this model, the link dynamics is the dominant evolutionary force shaping the statistical structure of the network, while the slower gene duplication dynamics mainly affects its size. Specifically, the model predicts (i) a broad distribution of the connectivities (i.e., the number of binding partners of a protein) and (ii) correlations between the connectivities of interacting proteins.

cond-mat.stat-mech↗

arXiv2004

Adaptive evolution of transcription factor binding sites

The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background) mutation rate, the selection coefficient, and the effective population size. The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.

cond-mat.stat-mech↗

arXiv2004

Local graph alignment and motif search in biological networks

Interaction networks are of central importance in post-genomic molecular biology, with increasing amounts of data becoming available by high-throughput methods. Examples are gene regulatory networks or protein interaction maps. The main challenge in the analysis of these data is to read off biological functions from the topology of the network. Topological motifs, i.e., patterns occurring repeatedly at different positions in the network have recently been identified as basic modules of molecular information processing. In this paper, we discuss motifs derived from families of mutually similar but not necessarily identical patterns. We establish a statistical model for the occurrence of such motifs, from which we derive a scoring function for their statistical significance. Based on this scoring function, we develop a search algorithm for topological motifs called graph alignment, a procedure with some analogies to sequence alignment. The algorithm is applied to the gene regulation network of E. coli.

cond-mat.stat-mech↗

arXiv2003

Modes of speciation in heterogeneous space

Modes of speciation have been the subject of a century's debate. Traditionally, most speciations are believed to be caused by spatial separation of populations (allopatry). Recent observations (Meyer 1990, Schliewen 1994, Schliewen 2001, Rico 2002) and models (MaynardSmith 1966, Antonovics 1971, Dickinson 1973, Rosenzweig 1978, T urner 1995, Noest 1997, Geritz 1998, Kondrashov 1999, Dieckmann 1999, Doebeli 2000, Slatkin 1980), show that speciation can also take place in sympatry. We discuss a comprehensive model of coupled differentiation in phenotype, mating, and space, showing that spatial segregation can be an induced process following a sympatric differentiation. This is found to be a generic mechanism of adaptation to heterogeneous environments, for which we propose the term diapatric speciation (Greek). It explains the ubiquitous spatial patching of newly formed species, despite their sympatric origin (Schliewen 1994, Schliewen 2001, Rico 2002).

cond-mat↗

arXiv2002

Correlated random networks

We develop a statistical theory of networks. A network is a set of vertices and links given by its adjacency matrix $\c$, and the relevant statistical ensembles are defined in terms of a partition function $Z=\sum_{\c} \exp {[}-β\H(\c) {]}$. The simplest cases are uncorrelated random networks such as the well-known Erdös-Rény graphs. Here we study more general interactions $\H(\c)$ which lead to {\em correlations}, for example, between the connectivities of adjacent vertices. In particular, such correlations occur in {\em optimized} networks described by partition functions in the limit $β\to \infty$. They are argued to be a crucial signature of evolutionary design in biological networks.

cond-mat.stat-mech↗